Article
Cell Biology
Katherine M. Bonefas, Christina N. Vallianatos, Brynne Raines, Natalie C. Tronson, Shigeki Iwase
Summary: Chromatin dysregulation is a major characteristic of neurodevelopmental disorders, particularly intellectual disability (ID) and autism spectrum disorders (ASD). The prevalence of ID and ASD is higher in males than females, with unknown reasons. A specific disorder called intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MRXSCJ) is caused by mutations in the lysine demethylase 5C (KDM5C) gene. While MRXSCJ was initially reported only in males, it is now understood that females with a heterozygous KDM5C mutation can also experience cognitive deficits. This study investigates the gene expression and behavioral abnormalities in female mice with a KDM5C mutation, providing valuable insights into the sex-dependent manifestation of neurodevelopmental disorders and the role of sex chromosomes.
Article
Biochemistry & Molecular Biology
Fatima S. Ugur, Mark J. S. Kelly, Danica Galonic Fujimori
Summary: The ARID domain of KDM5C is required for efficient nucleosome demethylation, while the PHD1 domain has an inhibitory role in KDM5C catalysis. XLID mutations adjacent to the ARID and PHD1 domains disrupt this regulation and lead to decreased demethylation activity. These findings reveal how XLID mutations affect the recognition and regulation of chromatin by KDM5C.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Genetics & Heredity
Po-Ming Wu, Wen-Hao Yu, Chi-Wu Chiang, Chen-Yu Wu, Jia-Shing Chen, Yi-Fang Tu
Summary: Two novel variations in the KDM5C gene were identified in two Chinese families with X-linked intellectual disability. The affected male patients exhibited severe intellectual disability, short stature, and facial dysmorphism. One patient with an additional variation also had epilepsy and autistic spectrum disorder. Transfection experiments showed reduced protein expression, stability, and histone demethylase activity. The literature review suggested that variations near the C-terminus of KDM5C were associated with autistic spectrum disorder.
NEUROLOGY-GENETICS
(2022)
Review
Plant Sciences
Huijia Kang, Tianyi Fan, Jiabing Wu, Yan Zhu, Wen-Hui Shen
Summary: Plants, as sessile organisms, are constantly exposed to diverse stresses, including pathogen invasion. Recent studies have found that pathogen infections can induce epigenetic changes in plants, leading to the reprogramming of plant defense genes. These mechanisms could be used in the design of stress-resistant plant varieties.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Chemistry, Medicinal
Yihui Song, Huiqing Zhang, Xiaoke Yang, Yuting Shi, Bin Yu
Summary: Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising epigenetic target for disease treatment. This review provides an update on LSD1 inhibitors, including natural products, synthetic compounds, and cyclic peptides reported in 2021. The design strategies, structure-activity relationships, binding model analysis, and modes of action are discussed. Highlights include the repurposing of FDA-approved drugs as reversible LSD1 inhibitors, the identification of clinical candidates for neuro-developmental disorders, and the enhanced anti-cancer effects of dual inhibitors targeting both LSD1 and HDAC6 or tubulin.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Hayden A. M. Hatch, Julie Secombe
Summary: The availability of genetic testing for individuals with neurodevelopmental disorders has emphasized the significance of genes crucial for nervous system development and function. KDM5C, a gene altered in Claes-Jensen syndrome, is known to regulate transcription through chromatin modification. While the genetic link between KDM5C and cognitive dysfunction is clear, further research is needed to understand how KDM5C controls transcriptional programs in neurons to impact growth and activity.
Article
Cardiac & Cardiovascular Systems
Raja Chakraborty, Allison C. Ostriker, Yi Xie, Jui M. Dave, Ana Gamez-Mendez, Payel Chatterjee, Yaw Abu, Jake Valentine, Kimberly Lezon-Geyda, Daniel M. Greif, Vincent P. Schulz, Patrick G. Gallagher, William C. Sessa, John Hwa, Kathleen A. Martin
Summary: This study reveals that p300 and CBP play distinct and opposing roles in VSMC phenotypic switching and co-regulate chromatin modifications through different functional interactions with TET2 or HDACs. Targeting specific histone acetyl-transferases may hold therapeutic promise for cardiovascular diseases.
Review
Endocrinology & Metabolism
Lindsay Moritz, Saher Sue Hammoud
Summary: This article explores the molecular mechanisms underlying male fertility and the process of chromatin remodeling. It points out the current gaps in understanding of the chromatin remodeling process and suggests future research directions to enhance our knowledge of the histone-to-protamine exchange and the etiology of idiopathic male infertility.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Sarah Larrigan, Sujay Shah, Alex Fernandes, Pierre Mattar
Summary: During brain development, the genome is repeatedly reconfigured to aid neuronal and glial differentiation, with a range of chromatin remodeling complexes facilitating the process. The non-redundancy of these complexes suggests a need for a variety of remodelers with different specificities and activities in neurodevelopment. The nucleosome remodeling and deacetylase (NuRD) complex plays a key role in the biochemistry, genetics, and functions of neural progenitors and neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Plant Sciences
Laura Poza-Viejo, Miriam Paya-Milans, Patxi San Martin-Uriz, Laura Castro-Labrador, David Lara-Astiaso, Mark D. Wilkinson, Manuel Pineiro, Jose A. Jarillo, Pedro Crevillen
Summary: Epigenetic regulation is crucial for optimal development and maintenance of gene expression profiles. This study uncovers the epigenetic mechanisms involved in flowering time regulation in Brassica rapa, shedding light on the conserved and distinct regulatory mechanisms between model and crop species.
PLANT CELL AND ENVIRONMENT
(2022)
Article
Cell Biology
Baoyu Chen, Yuwen Zhu, Junliang Chen, Yifei Feng, Yong Xu
Summary: This study reveals that differential TCL expression in malignant colorectal cancer cells is associated with histone H3K9 methylation, and the lysine demethylase KDM4B is essential for TCL transcription. KDM4B interacts with the transcription factor ERG1 to activate TCL transcription by facilitating the assembly of pre-initiation complex on the TCL promoter, ultimately influencing migration and invasion of CRC cells. Additionally, upregulation of KDM4B in advanced stage CRC specimens suggests it may serve as a potential therapeutic target for CRC intervention.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Saikat Bhattacharya, Divya Reddy, Ning Zhang, Hua Li, Jerry L. L. Workman
Summary: The methyltransferase SETD2 plays a crucial role in regulating transcription, splicing, and other processes through the deposition of the H3K36me3 histone mark. Its stability is controlled by proteasome-mediated degradation to maintain low levels. Excessive SETD2 leads to upregulation of cell cycle-associated pathways, resulting in increased cell proliferation and migration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Khadija D. Wilson, Elizabeth G. Porter, Benjamin A. Garcia
Summary: The etiology of neurodevelopmental disorders is complex and involves dysregulation of epigenetic regulation, including phenotypic overlap between different disorders. Studies have shown that chromatin regulation is closely associated with the occurrence of NDDs, which is important for understanding the disease mechanisms and therapies.
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Ziyu Zhang, Baoyu Chen, Yuwen Zhu, Tianyi Zhang, Yibiao Yuan, Xiaoling Zhang, Yong Xu
Summary: TGF-beta regulates the transcription of the prometastatic small GTPase RHOJ by activating MKL1 and recruiting the H3K9/H3K27 dual demethylase KDM7A. KDM7A can be used to predict prognosis in breast cancer patients and its knockdown attenuates migration, invasion, growth, and metastasis of breast cancer cells. KDM7A is a direct transcriptional target of TGF-beta signaling, and small-molecule inhibitors of KDM7A may provide therapeutic solutions for malignant breast cancers.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Zhenhui Zhong, Suhua Feng, Sascha H. Duttke, Magdalena E. Potok, Yiwei Zhang, Javier Gallego-Bartolom, Wanlu Liu, Steven E. Jacobsen
Summary: DNA methylation influences chromatin accessibility, particularly in heterochromatin, in plants. Different sequence contexts of DNA methylation interact with each other, and methylation can impact chromatin structure through mechanisms other than transcription. Increased chromatin accessibility is associated with enhanced long-range chromatin interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Geriatrics & Gerontology
Danielle D. Voigt, Caroline M. Nascimento, Ritiele B. de Souza, Pedro H. Cabello Acero, Mario Campos Junior, Camilla P. da Silva, Joao S. Pereira, Ana Lucia Rosso, Marco A. Araujo Leite, Luiz Felipe R. Vasconcellos, Marcus Della Colettai, Delson J. da Silva, Denise H. Nicaretta, Andressa P. Goncalves, Jussara M. dos Santos, Veluma Calassara, Cintia B. Santos-Reboucas, Marcia M. G. Pimentel
NEUROBIOLOGY OF AGING
(2019)
Article
Nutrition & Dietetics
Paula Normando, Cintia Santos-Reboucas, Cindy Leung, Elissa Epel, Ana Carolina da Fonseca, Veronica Zembrzuski, Eduardo Faerstein, Flavia F. Bezerra
Article
Genetics & Heredity
Cintia B. Santos-Reboucas, Raquel Boy, Evelyn Q. Vianna, Andressa P. Goncalves, Rafael M. Piergiorge, Bianca B. Abdala, Jussara M. dos Santos, Veluma Calassara, Filipe B. Machado, Enrique Medina-Acosta, Marcia M. G. Pimentel
FRONTIERS IN GENETICS
(2020)
Article
Neurosciences
Evelyn Quintanilha Vianna, Rafael Mina Piergiorge, Andressa Pereira Goncalves, Jussara Mendonca dos Santos, Veluma Calassara, Carla Rosenberg, Ana Cristina Victorino Krepischi, Raquel Tavares Boy da Silva, Suely Rodrigues dos Santos, Marcia Goncalves Ribeiro, Filipe Brum Machado, Enrique Medina-Acosta, Marcia Mattos Goncalves Pimentel, Cintia Barros Santos-Reboucas
MOLECULAR NEUROBIOLOGY
(2020)
Article
Psychiatry
Rafael Mina Piergiorge, Ana Tereza Ribeiro de Vasconcelos, Marcia Mattos Goncalves Pimentel, Cintia Barros Santos-Reboucas
Summary: This study identified new genes related to Intellectual Disability (ID) and Global Development Delay (GDD) through a stringent protein-protein interaction network analysis, expanding the understanding of the genetic landscape of these conditions and showing evidence of their close relationship at the molecular and functional levels.
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
(2021)
Article
Genetics & Heredity
Thiago Correa, Cintia B. Santos-Reboucas, Maytza Mayndra, Albert Schinzel, Mariluce Riegel
Summary: Chromosomal duplications are associated with a variety of human diseases, including intellectual disabilities. This study identified functional relationships among genes in duplicated chromosomal regions and demonstrated shared biological processes associated with intellectual disabilities between proteins from different chromosomal regions. The study also proposed a shared model of pathways related to the central nervous system that could disrupt cognitive function and lead to intellectual disabilities.
Article
Genetics & Heredity
Bianca Barbosa Abdala, Andressa Pereira Goncalves, Jussara Mendonca dos Santos, Raquel Boy, Claudia Marcia Benedetto de Carvalho, Christopher M. Grochowski, Ana Cristina Victorino Krepischi, Carla Rosenberg, Leonor Gusmao, Davut Pehlivan, Marcia Mattos Goncalves Pimentel, Cintia Barros Santos-Reboucas
Summary: MECP2 duplication syndrome (MDS) is a major cause of intellectual disability in males, characterized by copy number variations spanning the MECP2 gene at Xq28. Two unrelated males with non-recurrent complex Xq28 rearrangements associated with MDS were described in the study. Patient 1 inherited the rearrangement from the carrier mother, while patient 2 had a de novo unbalanced translocation originating in paternal gametogenesis. Both patients shared the core MDS phenotype, but differed in some details.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2021)
Article
Endocrinology & Metabolism
Thiago Correa, Fabiano Poswar, Cintia B. Santos-Reboucas
Summary: MPS II is a lysosomal storage disorder caused by mutations in the IDS gene, leading to GAGs accumulation and neurological symptoms. Research has identified genes and pathways in MPS II that affect early neural circuit formation defects, providing insights into cognitive impairment in patients.
METABOLIC BRAIN DISEASE
(2022)
Article
Endocrinology & Metabolism
Suely Rodrigues dos Santos, Rafael Mina Piergiorge, Jady Rocha, Bianca Barbosa Abdala, Andressa Pereira Goncalves, Marcia Mattos Goncalves Pimentel, Cintia Barros Santos-Reboucas
Summary: YY1 gene is a dual transcriptional activating and repressing factor, RNA-binding protein, and 3D chromatin regulator with multiple roles in neurodevelopmental pathways. Haploinsufficiency of YY1 due to heterozygous sequence variants or deletions can lead to Gabriele-de Vries syndrome, characterized by intellectual disability and physical/behavioral abnormalities. This study identified a de novo missense pathogenic variant in YY1 gene in a Brazilian female, expanding the understanding of the mutational and phenotype spectrum of GADEVS. Further analysis revealed potential implications for protein structure and function, as well as highlighted the role of YY1 in XCI epigenetic process.
METABOLIC BRAIN DISEASE
(2022)
Article
Genetics & Heredity
Cintia B. Santos-Reboucas, Raquel Boy, Gabriela N. S. Fernandes, Andressa P. Goncalves, Bianca B. Abdala, Lucas G. C. Gonzalez, Jussara M. dos Santos, Marcia M. G. Pimentel
Summary: This article reports a male patient with a novel duplication on Xp11.22, resulting in severe intellectual disability. The study also found increased levels of HUWE1 mRNA and different X-chromosome inactivation patterns in the carriers. The clinical, molecular, and neurological findings of this case expand the phenotype spectrum in Xp11.22 copy gains involving the HUWE1 gene in both males and female carriers.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Biology
Rafael Mina Piergiorge, Ronaldo da Silva Francisco Junior, Ana Tereza Ribeiro de Vasconcelos, Cintia Barros Santos-Reboucas
Summary: This study identified a complex ceRNA network involved in late-onset AD and highlighted the Fragile X Messenger Ribonucleoprotein 1 (FMR1) as a driver gene in this network. The findings enhance our understanding of ceRNA regulatory pathways in AD and provide potential targets for early biomarkers and therapeutic interventions.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Rheumatology
Jacyara Maria Brito Macedo, Amanda Lima Silva, Amanda Chaves Pinto, Leandro Ferreira Lopes Landeira, Elyzabeth Avvad Portari, Cintia Barros Santos-Reboucas, Evandro Mendes Klumb
Summary: This study found that TP53 and p21 gene polymorphisms are associated with the development of SLE. Different genotype combinations are also associated with clinical manifestations of SLE patients.
ADVANCES IN RHEUMATOLOGY
(2023)
Article
Pathology
Camilla Pereira da Silva, Diego Camuzi, Adriana Helena de Oliveira Reis, Andressa Pereira Goncalves, Jussara Mendonca dos Santos, Filipe Brum Machado, Enrique Medina-Acosta, Sheila Coelho Soares-Lima, Cintia Barros Santos-Reboucas
Summary: This pilot study investigated the methylation boundary and adjacent regions in FXS patients and found that a CpG site in FMR1 intron 2 could serve as a novel epigenetic biomarker for FXS diagnosis.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2023)
Article
Biochemistry & Molecular Biology
Orlando Louzada-Neto, Bruno A. Lopes, Gisele D. Brisson, Francianne G. Andrade, Ingrid S. Cezar, Cintia B. Santos-Reboucas, Rodolpho M. Albano, Maria S. Pombo-de-Oliveira, Ana Rossini
GENETICS AND MOLECULAR BIOLOGY
(2020)
Article
Biology
P. Normando, F. F. Bezerra, B. A. Santana, R. T. Calado, C. B. Santos-Reboucas, E. S. Epel, E. Faerstein
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
(2020)